Emerging evidence suggests that stressors at multiple levels are important predictors of psychopathology and behavior. Post-traumatic stress disorder (PTSD) and drug abuse/dependence are among the most prevalent and disabling behavioral pathologies. The purpose of this project is to determine whether ecologic stressors (concentrated disadvantage, income distribution, residential segregation, quality of the built environment), influence the risk of post-traumatic stress disorder (PTSD), and drug abuse/dependence among residents of Detroit. Additionally, we will begin to study the pathways linking ecologic stressors to long-term health through assessing the interrelationship among ecologic stressors, exposure to potentially traumatic events (PTEs), PTSD, drug abuse/dependence, and immune and inflammatory function. Our central hypothesis is that exposure to ecologic stressors is a fundamental determinant of population mental and behavioral health and that, particularly in the urban context, ecologic factors influence (a) the risk of PTE exposure, (b) the risk of PTSD given exposure to a PTE, (c) the risk of drug abuse/dependence, (d) the interrelationship between PTSD and drug abuse/dependence, and (e) some of the consequences of psychopathology. Although recent work has shown that stressors at multiple levels may be important determinants of psychopathology there has been very little systematic effort to understand the contributions of ecologic stressors to the risk of incident PTSD or drug abuse/dependence while also accounting for individual stressors. This project then aims to disentangle the contribution of stressors at multiple levels to the etiology of PTSD and drug abuse/dependence and how these stressors shape the relationship between these pathologies. Secondarily, we propose to consider the consequences of PTSD in the context of ecologic stressors, particularly the relation between PTSD and immune and inflammatory function, and how these consequences are shaped by exposure to ecologic stressors. Multilevel modeling principally will be used to evaluate whether ecologic stressors are associated with PTSD and drug abuse/dependence and to assess the relation among ecologic stressors, PTSD, immune functioning, and inflammatory measures.